The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis.
BACKGROUND
Cell-free fetal nucleic acids (cffNA) can be detected in the maternal circulation during pregnancy, potentially offering an excellent method for early non-invasive prenatal diagnosis (NIPD) of the genetic status of a fetus. Using molecular techniques, fetal DNA and RNA can be detected from 5 weeks gestation and are rapidly cleared from the circulation following birth.


METHODS
We searched PubMed systematically using keywords free fetal DNA and NIPD. Reference lists from relevant papers were also searched to ensure comprehensive coverage of the area.


RESULTS
Cell-free fetal DNA comprises only 3-6% of the total circulating cell-free DNA, therefore diagnoses are primarily limited to those caused by paternally inherited sequences as well as conditions that can be inferred by the unique gene expression patterns in the fetus and placenta. Broadly, the potential applications of this technology fall into two categories: first, high genetic risk families with inheritable monogenic diseases, including sex determination in cases at risk of X-linked diseases and detection of specific paternally inherited single gene disorders; and second, routine antenatal care offered to all pregnant women, including prenatal screening/diagnosis for aneuploidy, particularly Down syndrome (DS), and diagnosis of Rhesus factor status in RhD negative women. Already sex determination and Rhesus factor diagnosis are nearing translation into clinical practice for high-risk individuals.


CONCLUSIONS
The analysis of cffNA may allow NIPD for a variety of genetic conditions and may in future form part of national antenatal screening programmes for DS and other common genetic disorders.
Wright
Caroline F
CF
PHG Foundation Strangeways Research Laboratory, Cambridge, UK. caroline.wright@phgfoundation.org
Burton
Hilary
H
D000782:Aneuploidy; D004247:DNA / Q000097:blood*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D005333:Fetus; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D019849:Sex Determination Processes
D005819:Genetic Markers; D004247:DNA